CN101346438A - Amphipathic squarylium cyanine dyes, its preparation method and use thereof - Google Patents
Amphipathic squarylium cyanine dyes, its preparation method and use thereof Download PDFInfo
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- CN101346438A CN101346438A CNA2005800524082A CN200580052408A CN101346438A CN 101346438 A CN101346438 A CN 101346438A CN A2005800524082 A CNA2005800524082 A CN A2005800524082A CN 200580052408 A CN200580052408 A CN 200580052408A CN 101346438 A CN101346438 A CN 101346438A
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- 239000000975 dye Substances 0.000 title claims abstract description 72
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 title claims description 40
- 238000002360 preparation method Methods 0.000 title description 7
- IHXWECHPYNPJRR-UHFFFAOYSA-N 3-hydroxycyclobut-2-en-1-one Chemical compound OC1=CC(=O)C1 IHXWECHPYNPJRR-UHFFFAOYSA-N 0.000 claims abstract description 35
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- 239000007850 fluorescent dye Substances 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 11
- 238000003745 diagnosis Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 6
- 239000012530 fluid Substances 0.000 claims description 5
- 238000003018 immunoassay Methods 0.000 claims description 5
- 238000002372 labelling Methods 0.000 claims description 5
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- PWEBUXCTKOWPCW-UHFFFAOYSA-N squaric acid Chemical compound OC1=C(O)C(=O)C1=O PWEBUXCTKOWPCW-UHFFFAOYSA-N 0.000 claims description 5
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 238000004659 sterilization and disinfection Methods 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims 1
- 238000010898 silica gel chromatography Methods 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 4
- 239000000523 sample Substances 0.000 abstract description 2
- SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical compound NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 abstract 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 16
- 238000010521 absorption reaction Methods 0.000 description 14
- 238000011160 research Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000693 micelle Substances 0.000 description 9
- 239000003504 photosensitizing agent Substances 0.000 description 9
- 238000006862 quantum yield reaction Methods 0.000 description 9
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 7
- 230000005284 excitation Effects 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 229920004890 Triton X-100 Polymers 0.000 description 6
- 239000013504 Triton X-100 Substances 0.000 description 6
- 239000012736 aqueous medium Substances 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000001476 alcoholic effect Effects 0.000 description 4
- 125000002091 cationic group Chemical group 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000001857 fluorescence decay curve Methods 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 238000002428 photodynamic therapy Methods 0.000 description 4
- 230000004962 physiological condition Effects 0.000 description 4
- 238000004088 simulation Methods 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 239000001116 FEMA 4028 Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 3
- 229960004853 betadex Drugs 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- -1 30 °C Chemical compound 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- QISHCOOKKXNXNW-UHFFFAOYSA-M 1-ethyl-2-[7-(1-ethylquinolin-1-ium-2-yl)hepta-2,4,6-trienylidene]quinoline;iodide Chemical compound [I-].C1=CC2=CC=CC=C2N(CC)\C1=C\C=C\C=C\C=C\C1=CC=C(C=CC=C2)C2=[N+]1CC QISHCOOKKXNXNW-UHFFFAOYSA-M 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical group 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229960000800 cetrimonium bromide Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000001261 hydroxy acids Chemical group 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 208000017983 photosensitivity disease Diseases 0.000 description 1
- 231100000434 photosensitization Toxicity 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B57/00—Other synthetic dyes of known constitution
- C09B57/007—Squaraine dyes
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B69/00—Dyes not provided for by a single group of this subclass
Abstract
The present invention relates to amphiphilic squaraine dyes of the general formula (1) as shown below Formula (1) wherein, R<1> = -(CH2-CH2-O)n-CH3, n = 4-8, or -(CH2)n-CO2X, n = 3-6, X = H, succinamide and R<2> = -CH3 or -(CH2-CH2-O)n-CH3, n = 4-8 and pharmaceutically acceptable derivatives thereof, for use as near infrared fluorescence probes in photodynamic diagnostic and biological, biochemical and industrial applications.
Description
Technical field
The present invention relates in photodynamics diagnosis, biology, biological chemistry and industrial application the sour cyanines of amphipathic side (squaraine) dyestuff and the pharmaceutically acceptable derivative thereof of having as shown in the formula the general formula of (1) as near infrared fluorescent probe,
R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4-8, or-(CH
2)
n-CO
2X, n=3-6, X=H, succinoamino, and R
2=-CH
3Or-(CH
2-CH
2-O)
n-CH
3, n=4-8.
The invention still further relates to the method for the indolenium squaraine cyanine dye for preparing general formula 1 and the purposes that this sensitizing agent is used as the near infrared fluorescent probe in photodynamics, diagnosis and biology, biological chemistry and the industrial application.
The invention still further relates to indolenium squaraine cyanine dye or its pharmaceutically acceptable derivative of general formula 1, be used for using as near infrared fluorescent probe in the photodynamics that detects the intravital cancer of human or animal and other disease.
The invention still further relates to indolenium squaraine cyanine dye or its pharmaceutically acceptable derivative of general formula 1, as the near infrared fluorescent probe of biological applications.This research also relates to the indolenium squaraine cyanine dye of the general formula 1 of the near infrared fluorescent probe that can be used as protein labeling.This research also relates to the indolenium squaraine cyanine dye of the general formula 1 of the near infrared fluorescent probe that can be used as immunoassay.The invention still further relates to preparation is used for the light power industry and uses as the indolenium squaraine cyanine dye of the general formula 1 of the sterilization of fluid and water and relevant other application and/or the method for its derivative.
Background technology
Photodynamic therapy (PDT) is a kind of emerging form that is used for the diagnosis and the treatment of cancer and various diseases, and it relates to the comprehensive action of light and photosensitizers.Can be with reference to Lane, N.ScientificAmerican 2003,38-45; Bonnett, R.Chem.Soc.Rev.1995,24,19; Dougherty, T.J.Photochem.Photobiol.1987,45,879; Kessel, D.; Dougherty, T.J.Phorphyrin Photosensitization; Plenum Publishing Corp.New York, 1983.This method needs to be absorbed by destination organization and produces by the optical excitation of specific wavelength the time organizes the existence of the photosensitizer of virose material to these.Photodynamic therapy is owing to the selectivity of photodynamics method has the advantage that surpasses many routine treatments.Have in tumor tissues than the more photosensitizers of healthy tissues, this has reduced the possibility of destroying healthy tissues.In addition, light can be directed to especially target cell and tissue by utilizing optical fiber technology, this has further increased the selectivity of this method.Equally, before optical excitation not the employing of aitiogenic photosensitizer also significantly reduced side effect may.
In PDT, the detection of tumor tissues (diagnosis) is compared of equal importance with kill tumor cell (treatment).Near infrared (NIR) dyestuff has attracted considerable concern at present as the fluorescent probe of cancer detection.Can be with reference to Lin, Y.; Weissleder, R.; And Tung, C.H.Bioconjugate Chem.200213,605-610; Achilefu, S.; Jimenez, H.N.; Dorshow, R.B.; Bugal, J.E.; Webb, E.G.; Wilhelm, R.R.; Rajagopalan, R.; Johler, J.; Erion, J.L.J.Med.Chem.2002 45,2003-2015; Mujumdar, S.R.; Mujumdar, R.B.; Grant, C.M.; Waggoner, A.S.BioconjugateChem.1996,7,356-362.Because tissue is only transparent relatively for NIR, NIR fluorescence imaging (NIRF) and PDT can detect respectively and treat even surperficial tumour (subsurface tumor) down.Relevant therewith, the present invention is intended to develop the efficient near infrared absorption fluorescent probe based on indolenium squaraine cyanine dye that is used for biological applications.We have synthesized the dyestuff based on the sour cyanines structure in side, and it presents absorption in the near infrared region and emission and has gives their amphipathic substituting groups as carboxyl and ethylene glycol, thereby has improved its solubleness, fluorescence intensity and quickened the cell absorption.
In diagnostic techniques, as in the treatment technology, dyestuff is applied and makes it to distribute in vivo.But except tumor-selective, photosensitizers should show significant fluorescence volume under physiological condition.Therefore have strong absorption in the long wavelength zone, to the healthy tissues nontoxicity, may be dissolved in the damping fluid of physiological pH and the exploitation that shows the photosensitizer of higher curative effect is still and presses for.And because the needs of biological chemistry and biomedical applications, can also be extremely important as the design of the functional molecular of target with the particular cancer cell.
Our interest in this field comes from the thought of utilizing indolenium squaraine cyanine dye in photodynamics is used.The sour cyanines in side have constituted a class and have had the dyestuff of strong absorption band clearly red near infrared region.Their optical physics and spectrochemical property were in depth studied, because their absorption and photochemical properties make them be highly suitable for many industrial application.Can be with reference to United States Patent (USP) 6,001,523; 5,552,253; 5,444,463; Law, K.-Y.Chem.Rev.1993,93,449; Piechowski, A P; Bird, G.R.; Morel, D L.; Stogryn, E.L.J.Phy.Chem.1984,88,934.Our initial research shows, indolenium squaraine cyanine dye with heavy atom (as bromine and iodine) replace cause its compare with the parent indolenium squaraine cyanine dye in aqueous medium that solubleness increases and system between cross over efficient and strengthen.These dyestuffs reveal the absorption in the 600-620nm scope and demonstrate triplet excited state (Φ according to the different table of the character of halogen atom
T=0.22-0.5) and singlet oxygen (Φ (
1O
2The quantum yield of)=0.22-0.5).Use the cytotoxicity and the mutagenicity of mammalian cell and bacterial strain to studies show that these dye sheets reveal the remarkable cytotoxicity when exciting with visible rays, and its bioactive mechanism may be because the generation of external singlet oxygen.Can be with reference to Ramaiah, D.; Arun, K.T.; Das, S.and Epe, B. United States Patent (USP) 6,770,787B2 (2004), Ramaiah, D.; Arun, K.T.; Das, S.and Epe, B. indian patent 193540 (2004), Ramaiah, D.; Joy, A.; Chandrasekhar, N; Eldho, N.V.; Das, S.; George, M.V.Photochem.Photobiol.1997,65,783; Arun, K.T.; Ramaiah, D.; Epe, B.J.Phys.Chem.B 2002,107,11622, Ramaiah, D.; Eckert, I; Arun, K.T.; Weidenfeller, L.; Epe, B.Photochem.Photobiol.2002,76,672; Ramaiah, D.; Eckert, I; Arun, K.T.; Weidenfeller, L.; Epe, B.Photochem.Photobiol.2004,79,99.But the dyestuff that these heavy atoms replace has low-down fluorescence quantum yield (Φ in aqueous medium
F≤ 0.0003), thereby limited its fluorescent emission and detected application in the tumour (diagnosis) at the dyestuff by optionally being positioned tumor tissues.
In the present invention, novel dyestuff based on the sour cyanines in side is synthesized, and has proved their potentiality as near infrared fluorescent probe in biology, biological chemistry and the industrial application.
Goal of the invention
Main purpose of the present invention provides efficiently dyestuff and/or its pharmaceutically acceptable derivative based on the sour cyanines in side, as photosensitive dose of the near infrared in photodynamics diagnosis, biological chemistry and the industrial application.
Another object of the present invention provides efficiently dyestuff and/or its pharmaceutically acceptable derivative based on the sour cyanines in side, as the near infrared fluorescent probe in the photodynamics diagnosis that detects tumour.
Another object of the present invention provides efficiently dyestuff and/or its pharmaceutically acceptable derivative based on the sour cyanines in side, as the near-infrared fluorescent transmitter of biology, biological chemistry and industrial application.
Another purpose again of this research provides the dyestuff based on the sour cyanines in side of the near infrared fluorescent probe that can be used as protein labeling.
Another purpose again of this research provides the indolenium squaraine cyanine dye that can be used as the general formula 1 of the near-infrared fluorescent mark in the immunoassay.
Brief Description Of Drawings
In Figure of description
Fig. 1 general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3), general formula 2 (R wherein
1, R
2=-(CH
2-CH
2-O)
n-CH
3, n=4) and general formula 3 (R wherein
1=-(CH
2)
n-CO
2X, n=3, X=H and R
2=-CH
3) the absorption spectrum of indolenium squaraine cyanine dye in the 10%v/v ethanol water mixture.
Fig. 2 general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3), general formula 2 (R wherein
1, R
2=-(CH
2-CH
2-O)
n-CH
3, n=4) and general formula 3 (R wherein
1=-(CH
2)
n-CO
2X, n=3, X=H and R
2=-CH
3) the fluorescence emission spectrum of indolenium squaraine cyanine dye in the 10%v/v ethanol water mixture.
Fig. 3 general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) indolenium squaraine cyanine dye [CTAB] of variable concentrations a) 0 and g) emmission spectrum in the presence of the 129mM.Excitation wavelength 600nm.
Fig. 4 general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) indolenium squaraine cyanine dye [SDS] of variable concentrations a) 0 and e) emmission spectrum in the presence of the 21mM.Excitation wavelength 600nm.
Fig. 5 general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) indolenium squaraine cyanine dye [the Triton X-100] of variable concentrations a) 0 and g) emmission spectrum in the presence of the 118mM.Excitation wavelength 600nm.
Fig. 6 general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) the fluorescence decay curve figure of indolenium squaraine cyanine dye in 10% (vol/vol) ethanol-water mixture.(a) 10% (vol/vol) alcohol-water, (b) Triton X-100, (c) CTAB, (d) SDS and (L) lamp curve.Excitation wavelength 635nm.Emission wavelength 670nm.
Fig. 7 general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) indolenium squaraine cyanine dye [β-CD] of variable concentrations a) 0 and g) emmission spectrum in the presence of the 25mM.Excitation wavelength 600nm.
Fig. 8 general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) indolenium squaraine cyanine dye 10% (vol/vol) ethanol-water mixture in fluorescence decay curve figure.[β-CD] be 0 (b) 12mM and (L) lamp curve a).
Summary of the invention
Therefore, the present invention relates to squarylium cyanine dyes and pharmaceutically acceptable the deriving thereof of general formula 1 Thing.
Wherein, R1＝-(CH
2-CH
2-O)
n-CH
3, n=4-8, or-(CH2)
n-CO
2X, n=3-6, X=H, succinoamino; And R2＝-CH
3Or-(CH2-CH
2-O)
n-CH
3，n＝4-8。
In one embodiment of the invention, N-methyl-N-replaces or N, N-is disubstituted Aniline and squaric acid in the mixture of benzene and n-butanol (1: 1) with 2: 1 ratio at 90-100 The time of ℃ backflow 18-24h. Desolventizing obtains residue, and this residue carries out silicon then Plastic column chromatography is to obtain the compound of general formula 1.
Another embodiment of the present invention provides efficiently dyestuff and/or its pharmaceutically acceptable derivative based on the sour cyanines in side, as the near-infrared fluorescent transmitter of biology, biological chemistry and industrial application.
In another embodiment more of the present invention, the compound of formula 1 is used in the optical dynamic therapy as the near-infrared fluorescent transmitter of diagnosing cancer.
Another embodiment again of this research provides the dyestuff based on the sour cyanines in side of the near infrared fluorescent probe that can be used as protein labeling.
Another embodiment of this research provides the indolenium squaraine cyanine dye that can be used as the general formula 1 of the near-infrared fluorescent mark in the immunoassay.
Another embodiment compound of relating to formula 1 is as the purposes of the photosensitizers in the sterilization of fluid, water and relevant other industrial application again.
Embodiment
In this research, the indolenium squaraine cyanine dye of general formula 1 is synthesized, and studied its membrane simulation thing (as micella) (micelles) and medicament carrier system (as beta-cyclodextrin) exists and non-existent situation under photophysical property.In the preparation of the compound of general formula 1, the amino proton of aniline part is replaced by methyl, ethylene glycol and aliphatic carboxylic acid group.It is amphipathic that these dyestuffs are given in spent glycol and hydroxy-acid group modification expection, thereby improved permeability cell and produced target-specific.
The following examples provide in illustrational mode, therefore should not constitute limitation of the scope of the invention.
Embodiment 1-3 has described the typical synthetic method of the compound of general formula 1, and the compound that embodiment 4 and 5 has described general formula 1 the membrane simulation thing as neutral, negatively charged ion and cationic micelle and pharmaceutical carrier (as beta-cyclodextrin) exists and non-existent situation under photophysical property.
General formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) the preparation of indolenium squaraine cyanine dye.N-methyl-N-in the mixture of propyl carbinol and benzene (1: 3) (3,6,9,12-four oxa-tridecyls) aniline (400mg, 1.35mmol) and squaric acid (77mg, solution 0.67mmol) the component distillation backflow 18h by water.Solvent is depressurized and distills, and the residue that is obtained carries out chromatography on silica gel.Carry out the general formula 1 (R wherein that the post wash-out obtains 100mg (15%) with the mixture (1: 49) of methyl alcohol and chloroform
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) indolenium squaraine cyanine dye, mp 100-102 ℃;
1H NMR (300MHz, CDCl
3, 30 ℃, TMS): δ=3.21 (s, 6H ,-NCH
3), 3.37 (s, 6H ,-OCH
3), 3.72-3.52 (m, 32H ,-OCH
2), 6.81 (d, 4H, J=8.96, Ar-H), 8.39 (d, 4H, J=8.95Hz, Ar-H);
13C NMR (75MHz, CDCl
3, 30 ℃, TMS): δ=39.68,52.29,58.97,68.53,70.42,70.52,70.56,70.81,71.83,112.43,119.90,133.17,154.41,183.32,188.58; IR (Neat): v
Max2877,1610,1584,1140,1098cm
-1Ultimate analysis (%), C
36H
52N
2O
10Calculated value: C, 64.27; H, 7.79; N, 4.16; Measured value: C, 64.51; H, 7,69; N, 3.88.
General formula 2 (R wherein
1, R
2=-(CH
2-CH
2-O)
n-CH
3, the preparation of indolenium squaraine cyanine dye n=4).Two-(N, N-(3,6,9,12-four oxa-tridecyls)) aniline in the mixture of propyl carbinol and benzene (1: 3) (350mg, 0.74mmol) and squaric acid (42mg, solution 0.37mmol) passes through the component distillation backflow 18h of water.Solvent is depressurized and distills, and the residue that is obtained carries out chromatography on silica gel.Carry out the general formula 2 (R wherein that the post wash-out obtains 40mg (5%) with the mixture (1: 99) of methyl alcohol and chloroform
1, R
2=-(CH
2-CH
2-O)
n-CH
3, indolenium squaraine cyanine dye n=4), mp 78-80 ℃;
1H NMR (300MHz, CDCl
3, 30 ℃, TMS): δ=3.37 (s, 12H ,-OCH
3), 3.37-3.55 (m, 64H ,-OCH
2), 6.84 (d, 4H, J=8.96, Ar-H), 8.37 (d, 4H, J=8.95Hz, Ar-H);
13C NMR (75MHz, CDCl
3, 30 ℃, TMS): δ=50.73,58.91,68.31,70.38,70.49,70.53,71.80,111.54,115.85,129.15,147.60,183.32,188.58; IR (Neat): v
Max2918,2867,1610,1584,1114cm
-1Ultimate analysis (%), C
52H
84N
2O
18Calculated value: C, 60.92; H, 8.26; N, 2.73; Measured value: C, 61.20; H, 7,98; N, 2.49.
General formula 3 (R wherein
1=-(CH
2)
n-CO
2X, n=3, X=H and R
2=-CH
3) the preparation of indolenium squaraine cyanine dye.N-methyl-N-(carboxylic propyl group) aniline in the mixture of propyl carbinol and benzene (1: 3) (319mg, 1.74mmol) and squaric acid (100mg, 0.87mmol) the component distillation backflow 24h by water.Solvent is depressurized and distills, and the residue that is obtained carries out chromatography on silica gel.Carry out the general formula 3 (R wherein that the post wash-out obtains 100mg (13%) with the mixture (1: 9) of methyl alcohol and chloroform
1=-(CH
2)
n-CO
2X, n=3, X=H and R
2=-CH
3) indolenium squaraine cyanine dye, mp 238-240 ℃ (d);
1H NMR (300MHz, [D
6] DMSO, 30 ℃, TMS): δ=1.91 (p, 4H ,-CH
2), 2.40 (t, 4H, J=7.2Hz ,-CH
2), 2.91 (s, 6H ,-NH
3), 3.35 (t, 4H, J=7.3Hz ,-CH
2), 6.99 (d, 4H, J=9.07Hz, Ar-H), 8.05 (d, 4H, J=8.97Hz, Ar-H);
13C NMR (75MHz, [D
6] DMSO, 30 ℃, TMS): δ=21.82,31.41,38.46,52.03,112.64,116.73,129.17,149.13,179.23; IR (KBr): v
Max3420,2924,1729,1590,1439,1130cm
-1Ultimate analysis (%), C
26H
28N
2O
6Calculated value: C, 67.23; H, 6.08; N, 6.03; Measured value: C, 67.50; H, 5.81; N, 5.80.
People have great interest to the water-soluble near infrared probe that exploitation has the absorption in biological chromophore non-absorbent longer wavelength zone.Fig. 1 has shown the absorption spectrum of dyestuff in the 10%vol/vol ethanol-water mixture of general formula 1.As can be seen from the figure, these dyestuffs demonstrate the absorption peak that absorbs near the point of maximum value 640-645nm in the aqueous solution, and they demonstrate near the red shift of maximum value 640-645nm in as the alcoholic acid alcoholic solvent.Fig. 2 has shown the emmission spectrum of these dyestuffs in the 10%vol/vol ethanol-water mixture.These dyestuffs demonstrate in the aqueous solution fluorescent emission maximum value in the scope of 670-676nm, and the emission maximum in alcoholic solvent is in the scope of 660-665nm.These dyestuffs demonstrate in aqueous medium fluorescence quantum yield in the scope of 0.007-0.021, and in ethanol fluorescence quantum yield in the scope of 0.18-0.21.Absorption and emission maximum and the fluorescence quantum yield of these dyestuffs in water and alcoholic solvent listed in the table 1.Long-wavelength region absorption in aqueous medium and emission maximum and good fluorescence quantum yield make these dyestuffs become the ideal candidates person of the application of fluorescent probe.
Table 1
λ
max，nm λ
max，nm λ
max，nm
Absorb emission Φ
fAbsorb emission Φ
fAbsorb emission Φ
f
1 637 660 0.19 645 674 0.018 644 671 0.013
2 638 662 0.21 646 675 0.026 646 676 0.021
3 636 662 0.18 647 673 0.015 645 673 0.007
Stability and the research of photophysical property of photosensitizers under physiological condition is very important estimating that it is used for using in the various external or bodies.Particularly, (influence of β-CD) will provide the information of the relevant behavior of this photosensitizers under physiological condition for membrane simulation thing such as cetrimonium bromide (CTAB) and carrier system such as beta-cyclodextrin.In addition, this research also is used to clarify some main points, whether forms aggregate as particular dye under this environment and whether produces cytotoxic substance with it.These media are unique in its properties, because β-CD and enclosed molecule form inclusion complex, and other formation micellar structure, thereby hydrophobic and hydrophilic environment is provided simultaneously.
Fig. 3,4 and 5 has shown general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) the dyestuff emmission spectrum in the presence of cationic micelle CTAB, negatively charged ion micella SDS and neutral micelle Triton X-100 respectively.Along with the increase of micellar concentration, the fluorescence intensity of dyestuff increases, and has shown the effective interaction between micella and the dyestuff.For understanding the effect of micelle medium better, we have analyzed the psec time resolved fluorescence life-span of general formula 1 dyestuff.These dyestuffs demonstrate the single index decay when not having micella to exist, and demonstrate two exponential attenuatioies when having micella to exist.This two exponential attenuatioies when micella exists show two kinds of materials that spectroscopy is different of existence, a kind of dye molecule that comes from packing, and another kind comes from unconjugated dye molecule.Fig. 6 has shown general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) indolenium squaraine cyanine dye in the 10%vol/vol ethanol-water mixture and the fluorescence decay curve figure in the presence of cationic micelle CTAB, negatively charged ion micella SDS and neutral micelle Triton X-100.Table 2,3 and 4 has been listed general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3), general formula 2 (R wherein
1, R
2=-(CH
2-CH
2-O)
n-CH
3, n=4) and general formula 3 (R wherein
1=-(CH
2)
n-CO
2X, n=3, X=H and R
2=-CH
3) dyestuff cationic micelle CTAB, negatively charged ion micella SDS and neutral micelle Triton X-100 exist and non-existent situation under absorption and emission maximum, fluorescence quantum yield and life-span.These results show the ideal candidates person that these dyestuffs are near infrared sensors in the biological applications, and they will interact with membrane structure effectively in these are used.
Table 2
When formula exists at CTAB
Absorb emission lifetime,
λ
max，nm λ
max，nm Φ
f ps
1 642 663 0.12 560(45％)
920(55％)
2 644 667 0.096 410(25％)
1140(75％)
3 644 667 0.14 440(4％)
860(96％)
Table 3
When formula exists at SDS
Absorb emission lifetime,
λ
max，nm λ
max，nm Φ
f ps
1 640 663 0.15 590
2 643 668 0.16 690(4％)
1240(96％)
Table 4
When formula exists at Triton X-100
Absorb emission lifetime,
λ
max，nm λ
max，nm Φ
f ps
1 645 669 0.12 130(21％)
1120(90％)
2 646 671 0.14 450(7％)
1450
3 649 672 0.12 430(31％)
1140(69％)
Fig. 7 has shown general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) the emmission spectrum of dyestuff in the presence of β-CD.Similar to observed situation when micella exists, along with the increase of β-CD concentration, the emissive porwer of the indolenium squaraine cyanine dye of general formula 1 increases, and emission maximum demonstrates blue shift, shows the effective interaction between dyestuff and β-CD chamber.Fig. 8 has shown general formula 1 (R wherein
1=-(CH
2-CH
2-O)
n-CH
3, n=4 and R
2=-CH
3) dyestuff β-CD exist and non-existent situation under fluorescence decay curve, it demonstrates single index and decays when not having β-CD to exist.When β-CD exists, observe two exponential attenuatioies, show to have two types, a kind ofly come from the dye molecule that is encapsulated in β-CD chamber, and another kind comes from free dye molecule.Table 5 has been summarized absorption and emission maximum, fluorescence quantum yield and the life-span of the indolenium squaraine cyanine dye of general formula 1 under the situation that β-CD exists.These results clearly illustrate that these dyestuffs can use delivery system to be positioned on the specific target.
Table 5
When formula exists at β-CD
Absorb emission lifetime,
λ
max，nm λ
max，nm Φ
f ps
1 644 663 0.10 380(58％)
1470(42％)
2 645 668 0.07 610(83％)
1920(17％)
3 649 666 0.19 470(34％)
1600(66％)
Indolenium squaraine cyanine dye of the present invention has gratifying character as the near infrared fluorescent probe in photodynamics, diagnosis and biology, biological chemistry and the industrial application.
The main advantage of these systems comprises:
1. the squarylium cyanine dyes of formula 1,2 and 3 expressions is novel, pure one matters.
2. their synthetic method is very economical.
3. the squarylium cyanine dyes of formula 1,2 and 3 expressions has near infrared region (600-700nm) Absorption.
4. the squarylium cyanine dyes of formula 1,2 and 3 expressions has near infrared region (620-720nm) Emission.
5. the symmetrical squarylium cyanine dyes of formula 1,2 and 3 expressions has the emission quantum yield of 0.015-0.03 scope and increases near 10 times of (Φ in the presence of membrane simulation thing and pharmaceutical carrier in aqueous mediumF＝0.09-0.2)。
6. they can be used for photodynamics and use, such as the sterilization of fluid etc.
7. the party's acid cyanines radical dye can be used as the near infrared fluorescent probe of protein labeling.
8. the squarylium cyanine dyes of general formula 1 can be used as the near-infrared fluorescent mark in the immunoassay.
9. they are used in detection of biological important meals ion under the physiological condition.
10. these new dyes can be used as in biology, biochemistry and commercial Application closely The IR fluorescence sensor.
Claims (11)
1. the indolenium squaraine cyanine dye of general formula 1 and/or its pharmaceutically acceptable derivative,
Formula 1
Wherein, R
1=-(CH
2-CH
2-O)
n-CH
3, n=4-8, or-(CH
2)
n-CO
2X, n=3-6, X=H, succinoamino; And R
2=-CH
3Or-(CH
2-CH
2-O)
n-CH
3, n=4-8.
2. prepare the indolenium squaraine cyanine dye of general formula 1 and/or the method for its pharmaceutically acceptable derivative,
Formula 1
Wherein, R
1=-(CH
2-CH
2-O)
n-CH
3, n=4-8, or-(CH
2)
n-CO
2X, n=3-6, X=H, succinoamino; And R
2=-CH
3Or-(CH
2-CH
2-O)
n-CH
3, n=4-8,
This method comprises to be made that N-methyl-N-replaces or N, and disubstituted aniline of N-and squaric acid react in the mixture of benzene and propyl carbinol, and evaporating solvent and purifying residue, obtain the compound of formula 1.
3. according to the method described in the claim 2, wherein the ratio of mixture of benzene and propyl carbinol is 1: 1.
4. according to the method described in the claim 2, wherein temperature of reaction is in 90-110 ℃ scope.
5. according to the method described in the claim 2, wherein be reflected in 18-24 hour and finish.
6. according to the method described in the claim 2, wherein said purifying is realized by silica gel column chromatography, to obtain the compound of general formula 1.
7. the compound of formula 1 is as the purposes of the near-infrared fluorescent transmitter of photodynamics, diagnosis, biology, biological chemistry and industrial application.
The compound of formula 1 in the photodynamics that detects the intravital cancer of human or animal and other disease is used as the purposes of near infrared fluorescent probe.
9. the compound of formula 1 is as the purposes of the near infrared fluorescent probe of biological applications such as protein labeling.
10. the compound of formula 1 is as the purposes of the near-infrared fluorescent mark of immunoassay.
11. the compound of formula 1 is used for the purposes of light power industry application as sterilization and relevant other application of fluid and water.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2005/000457 WO2007077566A1 (en) | 2005-12-30 | 2005-12-30 | Amphiphilic squaraine dyes, process for preparation thereof and use thereof |
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| Publication Number | Publication Date |
|---|---|
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| CN101346438B CN101346438B (en) | 2012-05-23 |
Family
ID=37500034
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|---|---|---|---|
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Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20090068113A1 (en) |
| EP (1) | EP1966326B1 (en) |
| CN (1) | CN101346438B (en) |
| WO (1) | WO2007077566A1 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101915760A (en) * | 2010-07-07 | 2010-12-15 | 东华大学 | Method for detecting cysteine content in real time by colorimetric method |
| CN102575107A (en) * | 2010-01-15 | 2012-07-11 | 株式会社艾迪科 | Color tone correcting agent, squarylium compound and optical filter |
| CN102618086A (en) * | 2012-03-07 | 2012-08-01 | 东华大学 | Method for preparing trapezoidal broadband absorption carbene squaraine dye with one-step method |
| CN104774606A (en) * | 2015-03-27 | 2015-07-15 | 西北农林科技大学 | Production method of near infrared fluorescence probe for detecting avidin in aqueous buffer solution |
| CN104804466A (en) * | 2015-05-11 | 2015-07-29 | 福州大学 | Near-infrared outer squaraine dye modified with oxygen-ether chain as well as preparation method and application thereof |
| CN105001666A (en) * | 2015-07-20 | 2015-10-28 | 福州大学 | Asymmetric near-infrared squaraine dye, preparation method thereof and application thereof |
| WO2016154782A1 (en) * | 2015-03-27 | 2016-10-06 | Dow Global Technologies Llc | Squarylium compounds used for lcd color filters |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9985158B2 (en) | 2012-06-13 | 2018-05-29 | Massachusetts Institute Of Technology | Visibly transparent, luminescent solar concentrator |
| KR102087260B1 (en) | 2016-09-26 | 2020-03-10 | 삼성에스디아이 주식회사 | Novel compound, core-shell dye, photosensitive resin composition including the same, and color filter |
| KR102087259B1 (en) | 2016-09-28 | 2020-03-10 | 삼성에스디아이 주식회사 | Novel compound, core-shell dye, photosensitive resin composition including the same, and color filter |
| CN108070275B (en) * | 2016-11-10 | 2020-07-07 | 中国科学院化学研究所 | Squaric acid dye compound, preparation method and application |
| JP7077084B2 (en) * | 2018-03-16 | 2022-05-30 | 東友ファインケム株式会社 | Compound |
| CN109111384B (en) * | 2018-09-12 | 2020-10-09 | 常州大学 | 1, 2-symmetric squaraine probe based on mercury ion recognition and preparation method and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002212455A (en) * | 2000-12-28 | 2002-07-31 | Council Scient Ind Res | Heavy halogen atom-substituted squaraine-based dye, process for the prearation thereof, and use thereof as sensitizer for photodynamic, therapeutical and industrial applications |
| ES2233207B1 (en) * | 2003-11-17 | 2006-08-01 | Universidad Politecnica De Valencia | METHOD FOR THE DETECTION OF TIOLES IN AQUOUS SOLUTION. |
-
2005
- 2005-12-30 CN CN2005800524082A patent/CN101346438B/en not_active Expired - Fee Related
- 2005-12-30 US US12/097,489 patent/US20090068113A1/en not_active Abandoned
- 2005-12-30 EP EP05856287.7A patent/EP1966326B1/en not_active Not-in-force
- 2005-12-30 WO PCT/IN2005/000457 patent/WO2007077566A1/en active Application Filing
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102575107A (en) * | 2010-01-15 | 2012-07-11 | 株式会社艾迪科 | Color tone correcting agent, squarylium compound and optical filter |
| CN101915760A (en) * | 2010-07-07 | 2010-12-15 | 东华大学 | Method for detecting cysteine content in real time by colorimetric method |
| CN102618086A (en) * | 2012-03-07 | 2012-08-01 | 东华大学 | Method for preparing trapezoidal broadband absorption carbene squaraine dye with one-step method |
| CN102618086B (en) * | 2012-03-07 | 2013-12-11 | 东华大学 | Method for preparing trapezoidal broadband absorption carbene squaraine dye with one-step method |
| CN104774606A (en) * | 2015-03-27 | 2015-07-15 | 西北农林科技大学 | Production method of near infrared fluorescence probe for detecting avidin in aqueous buffer solution |
| WO2016154782A1 (en) * | 2015-03-27 | 2016-10-06 | Dow Global Technologies Llc | Squarylium compounds used for lcd color filters |
| CN104804466A (en) * | 2015-05-11 | 2015-07-29 | 福州大学 | Near-infrared outer squaraine dye modified with oxygen-ether chain as well as preparation method and application thereof |
| CN105001666A (en) * | 2015-07-20 | 2015-10-28 | 福州大学 | Asymmetric near-infrared squaraine dye, preparation method thereof and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1966326A1 (en) | 2008-09-10 |
| CN101346438B (en) | 2012-05-23 |
| EP1966326B1 (en) | 2014-04-23 |
| WO2007077566A1 (en) | 2007-07-12 |
| US20090068113A1 (en) | 2009-03-12 |
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